Rabies is a viral disease that is usually transmitted through the bite of an animal. Ribavirin, an antiviral drug, is a relatively new drug that might be able to manage rabies. [1,2].
Motivation and Background:
Animals such as dogs, foxes, wolves, and skunks can spread rabies. It is not common for humans to pass this disease to each other. Rabies has the highest fatality rate among infectious diseases. It is also the oldest and most feared disease among humans. There is a large incidence of rabies in developing countries because there is little control over domesticated animals and medical resources in those regions. Also, rabies occurs in rural areas, with children being its most frequent victims. In the United States, the highest incidence of this disease is in the west border of Texas, where the majority of animals are not domesticated. Rabies impacts the central nervous system, resulting in symptoms such as a fever and headaches. Other symptoms can include agitation, hallucinations, hydrophobia, and anxiety [3]. Usually, victims of rabies die days after the onset of these symptoms. In very rare cases, rabies patients have lived up to three weeks. Death by rabies is caused by severe neurological damage and the shutting down of organs.
Fig 1. Risk levels of being infected with rabies across the world in 2013
Ribavirin acts as a nucleoside inhibitor. It does this by resembling the nucleoside. The nuceloside that Ribavirin inhibits is guanosine. Guanosine is a purine nucleoside and is composed of a guanine attached to a ribose sugar. Since this target is not a protein like usual infectious disease targets, more time and resources needs to be allocated towards researching its interaction with the drug of interest. Size: molecular weight of the protein: Guanosine is not a protein. Its molecular weight is 283.241 grams per mole.
Location:
Guanosine is found in the cell nucleus and is always present as a part of an organism's genome.
Function in a normal cell:
The molecule's role as part of an organism's genome is important during replication of genetic material, transcription, and the capping of genetic material. These pathways are necessary for gene expression and the normal function of an organism's expressed proteins.
Fig 2. Schematic figure of guanosine
Drug Information:
Ribavirin was discovered in 1970 in a company that is today known as Valeant Pharmaceuticals. Its purpose then was to treat pediatric respiratory syncytial virus infections. Now, it is most commonly used against Hepatitis A, C, and B. In host cells, Ribavirin prevents replication, transcription, and capping of viral genetic material. In normal replication, transcription, and capping of viral genetic material, guanosine makes up a part of the sequence that codes for a specific protein to be produced. When Ribavirin "replaces" guanosine, the normal sequence of genetic material becomes interrupted.This interrupted sequence is then replicated in host cells. Since Ribavirin is not a part of the viral genetic material, the protein that will be translated from this sequence will not be the same as the protein coded by the sequence with guanosine. This process hinders viral function in host cells [6]. Ribavirin can also interact with Interleukin 2 (IL2), Interferon-gamma (IFN-γ) and Tumor Necrosis Factor-alpha (TNF-α). It has been proven that a treatment with Ribavirin will not result in any toxicity in the body. In addition to this, the drug caused an immune response in the brain. This shows that Ribavirin has a broad range of antiviral effects [3].Schematic figure of drug:
Fig 3. Schematic figure of Ribavirin
Formula: The molecular formula of Ribavirin is C8H12N4O5. Molecular weight: This molecule's molecular weight is 244.206 grams. CAS Number: Ribavirin's CAS number is 36791-04-5. Delivery method: This drug is taken orally. Side effects: Side effects of Ribavirin include diarrhea, dry mouth, nausea or vomiting, and weakness. It is important for women to not take Ribavirin when they are pregnant or when they are attempting to get pregnant. Their partners should also not take Ribavirin during this time. Also, if a child gets this drug prescribed to him, the dosage might change for the child due to a change in the child's weight [6]. Other names: Other names for Ribavirin include Rebetol, Copegus, Ribasphere, RibaPak, and Moderiba. Maker or company: Ribavirin is manufactured in many companies, including Genentech, Merck Sharp & Dome, and Kadmon Pharmaceuticals. Is it patented? This drug is patented. Clinical Trials Info: Clinical trials have been conducted for this drug. However, the majority of these clinical trials test the effect of Ribavirin on Hepatits C [5].
Origin: Ribavirin cannot be found in nature. This drug was synthesized in a lab and its origin may be ribonucleic acid. Alternatives to this drug: For managing and treating rabies, vaccination is the only alternative to the use of Ribavirin. In fact, vaccinations are the main defense against this disease today. Studies have shown that combination therapies involving the use of both vaccination and Ribavirin can be effective in managing rabies [4]. Miscellaneous: It is important to note that Ribavirin is not usually used to treat rabies. Its application to the management of this disease has been relatively recent. Using Ribavirin to treat a rabies patient is highly experimental. Because of this, more research needs to be conducted on the use of the drug. Other uses: As mentioned, Ribavirin can also be used to treat Hepatitis A, C, and B.
Disease/Drug of interest:
Rabies is a viral disease that is usually transmitted through the bite of an animal. Ribavirin, an antiviral drug, is a relatively new drug that might be able to manage rabies. [1,2].Motivation and Background:
Animals such as dogs, foxes, wolves, and skunks can spread rabies. It is not common for humans to pass this disease to each other. Rabies has the highest fatality rate among infectious diseases. It is also the oldest and most feared disease among humans. There is a large incidence of rabies in developing countries because there is little control over domesticated animals and medical resources in those regions. Also, rabies occurs in rural areas, with children being its most frequent victims. In the United States, the highest incidence of this disease is in the west border of Texas, where the majority of animals are not domesticated. Rabies impacts the central nervous system, resulting in symptoms such as a fever and headaches. Other symptoms can include agitation, hallucinations, hydrophobia, and anxiety [3]. Usually, victims of rabies die days after the onset of these symptoms. In very rare cases, rabies patients have lived up to three weeks. Death by rabies is caused by severe neurological damage and the shutting down of organs.References:
[1] Alan C. Jackson, Mary J. Warrell, Charles E. Rupprecht, Hildegund C. J. Ertl, Bernhard Dietzschold, Michael O'Reilly, Richard P. Leach, Zhen F. Fu, William H. Wunner, Thomas P. Bleck and Henry Wilde. Management of Rabies in Humans. Clinical Infectious Diseases. 2003, 36 (1), 60-63.
[2] guanosine.guanosine,https://pubchem.ncbi.nlm.nih.gov/compound/guanosine (accessed Feb 5, 2016).
[3] Peres, M. G. Ribavirin Has an In Vitro Antiviral Effect in Rabies Virus Infected Neuronal Cells but Fails to Provide Benefit in Experimental Rabies in Mice. Journal of Virology & Antiviral Research J Virol Antivir Res. 2013, 02 (2), 1-5.
[4] Rabies. Centers for Disease Control and Prevention, http://www.cdc.gov/rabies/.
[5] Ribavirin. Clinical Trials.gov, https://www.clinicaltrials.gov/ct2/results?term=ribavirin (accessed Feb 6, 2016).
[6] Ribavirin History. News-Medical.net, http://www.news-medical.net/health/ribavirin-history.aspx (accessed Feb 5, 2016).
External links:
http://www.cdc.gov/rabies/.https://www.clinicaltrials.gov/ct2/results?term=ribavirinhttp://www.news-medical.net/health/ribavirin-history.aspx
Target Information:
Ribavirin acts as a nucleoside inhibitor. It does this by resembling the nucleoside. The nuceloside that Ribavirin inhibits is guanosine. Guanosine is a purine nucleoside and is composed of a guanine attached to a ribose sugar. Since this target is not a protein like usual infectious disease targets, more time and resources needs to be allocated towards researching its interaction with the drug of interest.Size: molecular weight of the protein: Guanosine is not a protein. Its molecular weight is 283.241 grams per mole.
Location:
Guanosine is found in the cell nucleus and is always present as a part of an organism's genome.Function in a normal cell:
The molecule's role as part of an organism's genome is important during replication of genetic material, transcription, and the capping of genetic material. These pathways are necessary for gene expression and the normal function of an organism's expressed proteins.Drug Information:
Ribavirin was discovered in 1970 in a company that is today known as Valeant Pharmaceuticals. Its purpose then was to treat pediatric respiratory syncytial virus infections. Now, it is most commonly used against Hepatitis A, C, and B.In host cells, Ribavirin prevents replication, transcription, and capping of viral genetic material. In normal replication, transcription, and capping of viral genetic material, guanosine makes up a part of the sequence that codes for a specific protein to be produced. When Ribavirin "replaces" guanosine, the normal sequence of genetic material becomes interrupted.This interrupted sequence is then replicated in host cells. Since Ribavirin is not a part of the viral genetic material, the protein that will be translated from this sequence will not be the same as the protein coded by the sequence with guanosine. This process hinders viral function in host cells [6]. Ribavirin can also interact with Interleukin 2 (IL2), Interferon-gamma (IFN-γ) and Tumor Necrosis Factor-alpha (TNF-α). It has been proven that a treatment with Ribavirin will not result in any toxicity in the body. In addition to this, the drug caused an immune response in the brain. This shows that Ribavirin has a broad range of antiviral effects [3].Schematic figure of drug:
Formula:
The molecular formula of Ribavirin is C8H12N4O5.
Molecular weight: This molecule's molecular weight is 244.206 grams.
CAS Number: Ribavirin's CAS number is 36791-04-5.
Delivery method: This drug is taken orally.
Side effects:
Side effects of Ribavirin include diarrhea, dry mouth, nausea or vomiting, and weakness. It is important for women to not take Ribavirin when they are pregnant or when they are attempting to get pregnant. Their partners should also not take Ribavirin during this time. Also, if a child gets this drug prescribed to him, the dosage might change for the child due to a change in the child's weight [6].
Other names: Other names for Ribavirin include Rebetol, Copegus, Ribasphere, RibaPak, and Moderiba.
Maker or company: Ribavirin is manufactured in many companies, including Genentech, Merck Sharp & Dome, and Kadmon Pharmaceuticals.
Is it patented? This drug is patented.
Clinical Trials Info: Clinical trials have been conducted for this drug. However, the majority of these clinical trials test the effect of Ribavirin on Hepatits C [5].
Origin:
Ribavirin cannot be found in nature. This drug was synthesized in a lab and its origin may be ribonucleic acid.
Alternatives to this drug: For managing and treating rabies, vaccination is the only alternative to the use of Ribavirin. In fact, vaccinations are the main defense against this disease today. Studies have shown that combination therapies involving the use of both vaccination and Ribavirin can be effective in managing rabies [4].
Miscellaneous: It is important to note that Ribavirin is not usually used to treat rabies. Its application to the management of this disease has been relatively recent. Using Ribavirin to treat a rabies patient is highly experimental. Because of this, more research needs to be conducted on the use of the drug.
Other uses: As mentioned, Ribavirin can also be used to treat Hepatitis A, C, and B.